It is known that early detection of cancer is highly correlated with patient survival. Accordingly, research has focused on the discovery and recognition of new diagnostic biomarkers that relate to the presence of cancer, its severity, and its subsequent progression. Certain biomarkers are specific to certain cancer types, i.e., prostate specific antigen as a diagnostic marker for prostate cancer. However, other, non-specific biomarkers have value in early detection of cancer, determination of prognosis, monitoring of effectiveness of cancer treatment, detection of recurrence post-treatment, and the like. In this respect, it is known that various cytokines, growth factors, toxins, chemokines, and hormones are found in elevated concentrations at the onset of cancer and during metastasis of cancer.
One such cytokine is vascular endothelial cell growth factor (VEGF), also called vascular permeability factor (VPF). Vascular endothelial cell growth factor is an endothelial cell mitogen, and is known to be present in very small quantities in normal human blood in order to facilitate activities such as wound healing. In contrast, soluble VEGF is released in large quantities by tumorigenic cells (e.g. carcinomas of the breast, large and small intestine, pancreas, kidney, and the like) due to its critical role in angiogenesis. During angiogenesis, new blood vessels form from existing vessels to supply nutrients to the developing tumor cells. Due to VEGF's mitogenic nature, it facilitates the formation of the new blood vessels by selective action on endothelial cells.
Quantities of VEGF in serum and plasma of patients with tumors from a multitude of cancers (small-cell lung cancer, primary breast cancer, non-Hodgkin's lymphoma, prostate cancer, and the like) have been found to be significantly elevated. The concentration of VEGF has also been correlated with the presence of metastatic disease, disease stage in colorectal cancer, and poor prognosis in patients with small cell lung cancer.
Conventional assays for cytokines such as VEGF for use in detecting, diagnosing, or monitoring the progress or prognosis of cancer, or for monitoring treatment efficacy, generally rely on specific immunological assays for the protein. However, there is a need in the art for a more rapid screening method for early detection and monitoring of cancer. The screening method should be simple, reliable, and allow detection of indices of cancer such as VEGF and other analytes known to be produced in elevated quantities during onset, progression, and metastasis of various cancers.
The present invention satisfies this need in the art by providing methods and systems for detecting and monitoring cancer and its progression via detection and quantitation of a cytokine using a whole-cell biosensor. The invention relies on induction of permeability in the cell portion of the biosensor to detect and quantitate the cytokine.